Day and others have shown that approximately 20% of human tumor lines and viral transformed human lines are hypersensitive to alkylating agents due to an apparent absence of O to the sixth power-methylguanine methyltransferase. Since this "enzyme" acts as a suicide protein and is inactivated in the reaction with the damaged base, it is relatively abundant in normal cells - up to 10 to the sixth power per cell. If the defect in mer- cells is at the level of transcription, then mRNA species absent in mer+ cells could be enriched by hybridization subtraction procedures using cDNA probes from mer+ cells. In collaboration with R. Day and D. Yarosh, this has been done. Such probes have been used to screen a normal human cDNA library and a variety of cDNA clones have been isolated. We plan to further characterize such isolates by measuring the abundance in RNA from a variety of mer+ and mer- cell lines.